Until about 20 years ago, all known enzymes were proteins. But then it was discovered that some RNA molecules can act as enzymes; that is, catalyze covalent changes in the structure of substrates (most of which are also RNA molecules). Catalytic RNA molecules are called ribozymes.

The splicing reaction is self-contained; that is, the intron — with the help of associated proteins — splices itself out of the precursor RNA.

Once excision of the intron and splicing of the adjacent exons are completed, the story is over. In other words, although the action is catalyzed by the RNA, only a single molecule of substrate is involved (unlike protein enzymes that repeatedly catalyze a reaction).

However, synthetic versions of Group I introns made in the laboratory can — in vitro — act repeatedly; that is, like true enzymes.

The DNA of some Group I introns includes an open reading frame (ORF) that encodes a transposase-like protein that can make a copy of the intron and insert it elsewhere in the genome.

Spliceosomes remove introns and splice the exons of most nuclear genes. They are composed of 5 kinds of small nuclear RNA (snRNA) molecules and over 100 different protein molecules. It is the RNA — not the protein — that catalyzes the splicing reactions.

The molecular details of the reactions are similar to those of Group II introns, and this has led to speculation that this splicing machinery evolved from them.

Some viroidlike molecules get into the cell as passengers inside a conventional plant virus.
These are called virusoids or viroidlike satellite RNAs.

In both cases, the molecules consists of

single-stranded RNA whose

ends are covalently bonded to form a circle.

There are several regions where base-pairing occurs across adjacent portions of the molecule.

New viroids and virusoids are synthesized by the host cell as long precursors in which the viroid structure is tandemly repeated.

These repeats must be cut out and ligated to form the final product.

Most virusoids and at least one viroid are self-splicing; that is, they can cut themselves out of the precursor and ligate their ends without the aid of any host enzymes.

Thus they represent another class of ribozyme.

Both viroids and virusoids are responsible for a number of serious diseases of economically important plants; e.g. the coconut palm and chrysanthemums. (The problem is so severe with chrysanthemums that all growers in the U.S. now secure their stock from a few companies that raise the plants in "clean" rooms using stringent precautions to prevent infection by the viroid.)

The three-dimensional structure of the large (50S) subunit of a bacterial ribosome was published in August 2000. It clearly shows that formation of the peptide bond that links each amino acid to the growing polypeptide chain is catalyzed by the 23S RNA molecule in the large subunit. The 31 proteins in the subunit probably provide the scaffolding needed to maintain the three-dimensional structure of the RNA.

In today's world, RNA polymerases — made of protein — make the RNA molecules (using the antisense strand of DNA as a template [View]). Could RNA alone have done it?

It can be done in the laboratory. Wochner, A. et al. report in Science, 332:209, 8 April 2011, their creation of a synthetic RNA molecule that when presented with single-stranded RNA templates, polymerizes ribonucleotide triphosphates into strands of RNA complementary to the template. Their synthetic RNA polymerase was able to faithfully incorporate up to 95 nucleotides into complementary strands of RNA. One product was a functional endonuclease ribozyme. (By the autumn of 2013, they were able to copy a template of 206 nucleotides.)

The ability of ribozymes to recognize and cut specific RNA molecules makes them exciting candidates for human therapy. Already, a synthetic ribozyme that destroys the mRNA encoding a receptor of Vascular Endothelial Growth Factor (VEGF) is being readied for clinical trials. VEGF is a major stimulant of angiogenesis, and blocking its action may help starve cancers of their blood supply.